Jr. Tormo et al., gamma-Lactone-functionalized antitumoral acetogenins are the most potent inhibitors of mitochondrial complex I, BIOORG MED, 11(5), 2001, pp. 681-684
To study the relevance of the terminal alpha,beta -unsaturated gamma -methy
l-gamma -lactone moiety of the antitumoral acetogenins of Annonaceae for po
tent mitochondrial complex I inhibition, we have prepared a series of semis
ynthetic acetogenins with modifications only in this part of the molecule,
from the natural rolliniastatin-1 (1) and cherimolin-1 (2). Some of the hyd
roxylated derivatives (1b, 1d and 1e) in addition to two infrequent natural
beta -hydroxy gamma -methyl gamma -lactone acetogenins, laherradurin (3) a
nd itrabin (4), are more potent complex I inhibitors than any other known c
ompounds. (C) 2001 Elsevier Science Ltd. All rights reserved.